Scientific Reports (Jul 2017)

Concise and Stereodivergent Synthesis of Carbasugars Reveals Unexpected Structure-Activity Relationship (SAR) of SGLT2 Inhibition

  • Wai-Lung Ng,
  • Ho-Chuen Li,
  • Kit-Man Lau,
  • Anthony K. N. Chan,
  • Clara Bik-San Lau,
  • Tony K. M. Shing

DOI
https://doi.org/10.1038/s41598-017-05895-9
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 8

Abstract

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Abstract Carbasugar sodium-glucose cotransporter 2 (SGLT2) inhibitors are highly promising drug candidates for the treatment of Type 2 diabetes mellitus (T2DM). However, the clinical usage of carbasugar SGLT2 inhibitors has been underexplored, due to the lengthy synthetic routes and the lack of structure-activity relationship (SAR) studies of these compounds. Herein, we report a concise and stereodivergent synthetic route towards some novel carbasugar SGLT2 inhibitors, featuring an underexploited, regioselective, and stereospecific palladium-catalyzed allyl-aryl coupling reaction. This synthetic strategy, together with computational modeling, revealed the unexpected SAR of these carbasugar SGLT2 inhibitors, and enabled the discovery of a highly selective and potent SGLT2 inhibitor.